Other Therapies

High-dose chemotherapy with stem cell support.

High-dose chemotherapy with stem cell support.

Ewing 2008R3 (NCT00987636) was the first phase III, open-label, multicenter, randomized controlled trial conducted for newly diagnosed patients with disseminated Ewing sarcoma who had metastases to bone and/or other sites.[24][Level of evidence B1] The study evaluated the EFS and OS effect of treatment with treosulfan and melphalan high-dose chemotherapy (TreoMel-HDT) followed by infusion of autologous hematopoietic stem cells. After six cycles of chemotherapy (vincristine, ifosfamide, doxorubicin, and etoposide), consenting patients were randomly assigned to receive either eight cycles of consolidation therapy (vincristine, dactinomycin, and cyclophosphamide) or consolidation therapy with TreoMel-HDT followed by autologous stem cell reinfusion. Between 2009 and 2018, 109 patients were randomly assigned, 55 of whom received TreoMel-HDT. There was no significant difference in 3-year EFS rates between patients who received TreoMel-HDT and patients in the control arm (20.9% vs. 19.2%; median follow-up, 3.3 years).

High-dose chemotherapy with stem cell support.

One of the largest studies was the EURO-EWING-INTERGROUP-EE99 R3 trial that enrolled 281 patients with primary disseminated metastatic Ewing sarcoma. Patients were treated with six cycles of vincristine, ifosfamide, doxorubicin, and etoposide followed by high-dose therapy and autologous stem cell transplant. Patients had a 3-year EFS rate of 27% and an OS rate of 34%. Identified independent prognostic factors included the presence and number of bone lesions, primary tumor volume greater than 200 mL, age older than 14 years, additional pulmonary metastases, and bone marrow involvement.[3][Level of evidence C2]

High-dose chemotherapy with stem cell support.

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial. Among patients with isolated pulmonary metastases, there was no difference in 3-year EFS rates (55.7% with BuMel vs. 50.3% with continued chemotherapy and whole-lung radiation therapy; P = .21).[25]

Melphalan. At nonmyeloablative doses, melphalan proved to be an active agent in an up-front window study for patients with metastatic disease at diagnosis. However, the cure rate remained extremely low.[26]

Irinotecan. Irinotecan was administered as a single agent in an up-front window study for patients with newly diagnosed metastatic Ewing sarcoma and showed modest activity (partial response in 5 of 24 patients).[27][Level of evidence C3] Further investigation is needed to determine irinotecan dosing and combinations with other agents for patients with Ewing sarcoma.